Hyposalivation and xerostomia (commonly referred to as ‘dry mouth’) are relatively common among a variety of people, and are especially common among the elderly, patients taking various medications (e.g., chemotherapeutic agents, antihistamines, antidepressants, diuretics, medical marijuana, cannabinoids, etc.), and individuals with high coffee or alcohol consumption. Xerostomia is also often found in patients with endocrine disorders, nutritional deficiencies, nerve damage to the face, neck, and head, and even stress. Most typically, patients suffering from hyposalivation and/or diagnosed with xerostomia, including those with Sjogren's Syndrome will have a noticeable and significant reduced flow and volume of saliva, commonly also associated with chemical changes in the saliva, all of which often presents itself in a variety of symptoms, including bad breath, thick and string-like saliva, an altered sense of taste and, in some cases, difficulty speaking or swallowing. In more severe cases, xerostomia is also associates with oral infections, sores or cracked tissue along the corners of the mouth.
Non-Sjogren's or rheumatoid/inflammatory disease suffers are more likely to have intermittent discomfort associated with a noticeable paucity of saliva. Eighty percent of all instances of hyposalivation are directly attributable to the use of prescription drugs or over the counter medications known to interact with the central nervous system. However, even otherwise healthy individuals experience periods of hyposalivation, typically associated with high stress, physical exhaustion, speaking nervousness, or diurnal effects of hormones. For example, many individuals experience periods of hyposalivation while sleeping as mastication and general stimulation to the salivary glands is reduced during this time. While most individuals can ignore transient hyposalivation or mask it's effects by increasing water consumption, it is preferable to avoid it, if possible. Overall oral comfort is associated with sufficient saliva to create a feeling of moisture, lubrication, hydration of the soft tissues, and the ability to move the tongue and speak, swallow, and chew without discomfort. The average resting flow rates for a healthy adult are generally recognized to be about 1.5 ml per minute. When an individual's salivary output drops to about 50% of their normal resting flow, they are more likely to notice hyposalivation and its effects on their oral comfort.
There are many compositions and methods known for the treatment of xerostomia. For example, U.S. Pat. No. 4,980,177 teaches mechanical stimulation with a chewing gum that further includes hydrophilic compounds. Similarly, U.S. Pat. No. 4,997,654 teaches a chewing gum formulation with relatively high xylitol content to promote salivation and U.S. Pat. No. 6,656,920 teaches use of disaccharides in a composition to treat xerostomia. Alternatively as described in U.S. Pat. No. 4,820,506, an organic acidulant and sweetener are used to promote saliva production and/or flow. Similarly, WO 89/09594 teaches use of an organic acid in a controlled release chewing gum formulation, and U.S. Pat. App. No. 2006/0204551 teaches a synergistic combination of a food acid and a tingling sensate to promote salivation. While such compositions tend to provide at least some relief to a patient, several disadvantages nevertheless remain. For example, use of chewing gum is typically not recommended overnight and thus often limited to daytime use. Moreover, and especially where acids are employed, prolonged exposure may result in at least partial dental demineralization.
To avoid at least some of these problems, nutritionally acceptable and chemically defined compounds may be administered as described in U.S. Pat. App. No. 2007/0128284 where a sulfur-containing antioxidant such as N-acetylcysteine is combined with a polymeric base, or in U.S. Pat. App. No. 2004/0076695 where omega-3 fatty acids are used, in various compositions. In yet further known compositions, peroxidized lipids (typically plant oils) and silica are used to alleviate xerostomia as taught in U.S. Pat. App. No. 2006/0078620. In yet other known methods, glycerol may be employed to improve dry mouth conditions as noted in U.S. Pat. App. No. 2009/0263467A1. Still further known compositions include those in which certain plant extracts are used to formulate a composition for treatment of xerostomia as described in U.S. Pat. No. 4,938,963 (Yerba Santa extract) and U.S. Pat. No. 6,746,697 (Heliopsis Longipes extract). Yet further known compositions and methods are described in WO 2007/092811.
While at least some of these compositions can potentially provide temporary relief in a patient, several disadvantages nevertheless remain. For example, the chemical stability of some of the compounds (and even some of the plant extracts) may be problematic. Moreover, and depending on the particular formulation, the obtained effect is relatively weak and thus requires repeated administration and/or high concentration of the active ingredient, which may be prohibitive due to bad taste or solubility.
Medical marijuana has been used to treat a vast array of medical conditions. Recently legalization for recreational use has been the subject of debate. Regardless of the use there are a number of different side effects associated with administering marijuana. One of these is dry mouth or cottonmouth. Once believed to be caused by the hot smoke inhaled when smoking cannabis, it is now believed to be more directly related to the consumption of cannabis. In fact, the submandibular glands where saliva and amylase are produced contain the CB1 and CB2 cannabinoid receptors. Activation of these cannabinoid receptors occurs whenever every time cannabis is consumed, thus producing dry mouth. In certain compositions of medical marijuana, the active agent THC is removed, yet other cannabinoids are still present, hence the potential for hyposalivary effects of use when ingested, smoked, or otherwise used in the human body. Activation of the M3 receptors for the salivary glands allows for release of saliva when cannaboid mediated suppression is present.
Hard and Soft tissue impacts of hyposalivation are understood, including the severe levels of hyposalivation seen with chronic medically indicated Cannabis consumption, and include: loss of cellular and epithelial protection of a mucin containing coating over such soft tissues of the mouth, oral mucositis or inflammation of the soft tissues, fissuring or cracking of the dorsal and lateral surfaces of the tongue, glossitis, burning mouth syndrome, demineralization of teeth and caries especially of the coronal aspect, and sensitivity resulting from the loss of the protective cementum, dentin, or enamel of the surface of a tooth, and increased propensity of tooth loss, attachment loss, gingivitis, and halitosis.
A recent article in Journal of the American Dental Association, (Dental treatment planning considerations for patients using cannabis, Sarah Essek Grafton, DMD, Po Ning Huang, DMD Candidate, BS, Alexandre R. Vieira, DDS, MS, PhD, JADA May 2016 Volume 147, Issue 5, Pages 354-361) reported cases of gingivitis linked directly to chronic use of Cannabis. The study shared that gingivitis was associated with use of Cannabis and that dentists needed to be both aware of the association and proper treatment.
The oral tissue impacts of severe hyposalivation are painful physiologically and psychologically, expensive to treat, and can lead to severe systemic impacts such as major whole body inflammation, infection, cardiovascular, metabolic, and nutritional outcomes including the potential disability and loss of life.
Pharmaceutical companies are recognizing the health benefits afforded by use of THC and other cannabinoids for a variety of conditions including chronic pain relief, MS, arthritis, AIDS, Alzheimer's, asthma, cancer, epilepsy, glaucoma. The discovery and development of more traditional pharmaceutically standardized and modified forms of cannabinoid compounds, holds great promise but not without side effects including hyposalivation caused by activation of the CB1 and CB2 receptors found in the major salivary glands of the mouth. At this point the pharmaceutical development of cannabinoids has not found a method or way to modify the actives to avoid this serious outcome of use of otherwise beneficial drugs. It is widely accepted that cannabinoids including cannabis are causative of temporary hypo salivation and that relief of this condition is a desired state.
Therefore, while numerous compositions and methods to reduce symptoms of xerostomia and/or hyposalivation are known in the art, there is still a need to provide improved compositions and methods for alleviation of symptoms associated with xerostomia and/or hyposalivation, and promote overall oral comfort/feel in the general population especially those using cannabinoids in any fashion.